A number of treatment approaches have been advocated for persistent visual complaints following mild traumatic brain injury. These include devices such as binasal occlusion, yoked prisms, vertical prisms, and filters, as well as vestibular training. We discuss the rationale and the evidence for each of these approaches. Binasal occlusion has been advocated for visual motion sensitivity, but it is not clear why this should help, and there is no good evidence for its symptomatic efficacy. Base-in prisms can help manage convergence insufficiency, but there are few data on their efficacy. Midline shift is an unproven concept, and while the yoked prisms advocated for its treatment may have some effect on egocentric neglect, their use in mild traumatic brain injury is more questionable. A wide variety of posttraumatic symptoms have been attributed to vertical heterophoria, but this is an unproven concept and there are no controlled data on the use of vertical prisms for mild traumatic brain injury symptoms. Filters could plausibly ameliorate light intolerance but studies are lacking. Better evidence is emerging for the effects of vestibular therapy, with a few randomized controlled trials that included blinded assessments and appropriate statistical analyses. Without more substantial evidence, the use of many of these techniques cannot be recommended and should be regarded as unproven and in some cases implausible.The pathological character of cerebral small vessel disease (CSVD) is the dysfunction of cerebral small arteries caused by risk factors. A switch from the contractile phenotype to the synthetic phenotype of vascular smooth muscle cells (SMCs) can decrease the contractility of arteries. The alteration of the vascular wall extracellular matrix (ECM) is found to regulate the process. We speculated that SMCs phenotype changes may also occur in CSVD induced by hypertension and the alteration of ECM especially fibronectin and laminin may regulate the process.
Male spontaneously hypertensive rats (SHR) were used as a CSVD animal model. SMCs phenotypic markers and the ECM expression of the cerebral small arteries of SHR at different ages were evaluated by immunofluorescence. The phenotype changes of primary brain microvascular SMCs cultured on laminin-coating dish or fibronectin-coating dish were evaluated by western blot.
A switch from the contractile phenotype to synthetic phenotype in SHR at 10 and 22weeks of age was observed. Meanwhile, increased expression of fibronectin and a temporary decline of laminin was found in small arteries of SHR at 22weeks. In vitro experiments also convinced that SMCs cultured on a fibronectin-coating dish failed to maintain contractile phenotype. While at 50weeks, significant drops of both synthetic and contractile phenotypic markers were witnessed in SHR, with high expressions of four kinds of ECM.
SMCs in cerebral small arteries exhibited a switch from the contractile phenotype to synthetic phenotype during the chronic process of hypertension and aging. https://www.selleckchem.com/products/mk-8353-sch900353.html Moreover, the change of fibronectin and laminin may regulate the process.
SMCs in cerebral small arteries exhibited a switch from the contractile phenotype to synthetic phenotype during the chronic process of hypertension and aging. Moreover, the change of fibronectin and laminin may regulate the process.Phospholipids are amphiphilic lipids with versatile properties making them promising excipients for enabling formulations for oral drug delivery. Unfortunately, systematic studies on how phospholipid type and content affect oral absorption are rare. Often, only one phospholipid type is used for the formulation development and only one formulation, optimized according to in vitro parameters, is included in oral bioavailability studies. Using this approach, it is unclear if a certain in vitro parameter is predictive for the in vivo performance. In this study, a labor-saving in vitro permeation screening method was combined with a pharmacokinetic study in rats to for the first time systematically compare two types of phospholipid-based solid dispersions. The dispersions contained the drug celecoxib and monoacyl or diacyl phosphatidylcholine at different drug-to-phospholipid ratios. The in vitro screening revealed 1) none of the formulations with high phospholipid content increased permeation, 2) phospholipid content was negatively correlated with permeation, and 3) mono and diacyl-phosphatidylcholine formulations performed equally. The pharmacokinetic study revealed 1) At low phospholipid content absorption was enhanced, 2) phospholipid content was negatively correlated with absorption, and 3) monoacyl and diacyl phosphatidylcholine formulations performed equally. Apart from the reference (suspension), the in vitro permeation screening thus predicted the formulations in vivo performance.In this study, the lack of complete drug release from amorphous solid dispersions (ASDs), as observed in most published reports, was investigated. ASDs with 20% ritonavir were prepared by HME using polyvinylpyrrolidone vinyl acetate (PVPVA) alone and in combination with 10% poloxamer 407 or Span 20 as carriers. It was established by the film casting technique that ritonavir was molecularly dispersed in formulations, and accelerated stability testing confirmed that extrudates were physically stable. Dissolution of ASDs (100-mg ritonavir equivalent) was performed in 250 mL 0.01 N HCl (pH 2), pH 6.8 phosphate buffer and FeSSIF-V2. Drug concentrations were measured by filtration through 0.45-μm pores and in unfiltered media; the latter gave total amounts of drug present in dissolution media, both as solution and dispersion. Because of low solubility, ritonavir did not dissolve completely in aqueous media. Rather, it formed supersaturated solutions, and the excess drug dispersed in the oily amorphous form with low particle sizes that could crystallize with time. Due to higher drug solubility, the dissolved drug in FeSSIF-V2 was much higher than that in the phosphate buffer. Complete drug release could be observed by accounting for drug both in solution and as phase-separated dispersion. Thus, the present study provides a complete picture of in vitro drug dissolution and dispersion from ASDs.